The antibiotic Clindamycin (Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside) and its pharmaceutically acceptable salts were originally disclosed and claimed in U.S. Pat. No. 3,580,904 (U.S. Pat. No. '904). The U.S. Pat. No. '904 patent also exemplify a pharmaceutical antibacterial syrup preparation and a method of using it to treat antibacterial diseases. The U.S. Pat. No. 3,655,885 discloses the pediatric syrup formulations for treating lincomycin susceptible bacterial infections.
Clindamycin is a lincosamide antibiotic. It is a semisynthetic antibiotic produced by a 7(S)-chloro substitution of the 7(R)-hydroxyl group of the parent compound lincomycin. Clindamycin is used primarily to treat infections caused by susceptible anaerobic bacteria, including infections of the respiratory tract, septicemia and peritonitis. Clindamycin is also used to treat aerobic bacterial infections and also used to treat some protozoal diseases, such as malaria.
Oral administration constitutes a preferred route for administering Clindamycin. This route is convenient and acceptable to the patients. Conventional dosage forms like tablet, pill, and capsule constitute the solid dosage forms for oral administration. Unfortunately, such formulations may be associated with certain disadvantages such as administering drug formulations to pediatric and geriatric patients, who either may dislike such compositions or may have problem in swallowing. In such situations, oral liquid dosage forms are the preferred choice. However, these dosage forms usually lead to perceptible exposure of the active drug ingredient to the taste buds, which is a very serious problem when the drug has an extremely unpleasant or bitter taste.
The unpleasant taste of the drugs, which are orally administered, is disadvantageous in several aspects. Taste is an important parameter governing the compliance. The disagreeable and unpleasant taste of drugs causes difficulties in swallowing or causes patients to avoid their medication, thereby resulting in low patient compliance. Thus taste-masking technologies are considered important and are developed by many researchers.
U.S. Pat. No. 6,806,256, describes a taste masked oral solution for quinolone-carboxylic acid antibiotic containing sucralose, sugar sweetener and at least one flavoring agent.
US 20080008765 describes taste-masked composition for oral administration of ready to use suspension containing coated particles in a suspension base.
U.S. Pat. No. 5,730,997 describe an oral liquid formulation for antitussives, antihistamines, decongestants, expectorants and mixtures thereof using a high osmolarity system.
Clindamycin like many drug substances has an inherently unpleasant taste (taste and after taste) and odour. This constitutes a significant disadvantage with the existing oral liquid compositions. It is a well-known fact that patients' compliance is low when oral preparations are presented with unpleasant taste and odour.
Artificial flavorings and sweeteners have often been used to mask the taste by generally overwhelming the taste of the pharmaceutical. However, these are often inadequate and the bitter taste remains as a lingering after taste. Other methods of masking the taste include coating the drug with a polymeric material such as ethyl cellulose or an oil, lipid or wax such as paraffins, waxes, beeswax, higher fatty acids, higher fatty acid esters, glycerin fatty acid esters or lecithin, so as to create a barrier and delay the dissolution of the drug. These methods however suffer from the disadvantage of process and formulation complexity and though sometimes suitable for solid dosage forms, in liquid formulations the drug is usually solubilized sufficiently to impart an unpleasant taste. For many drugs, there is an unpleasant taste when dissolved in water-based formulations. Oil-based vehicles are generally not satisfactory for the reason of poor mouth feel and risk of altered bioavailability.
Numerous liquid pharmaceutical compositions for oral administration of clindamycin have been proposed, however there still exists a need for stabilized clindamycin composition with improved taste, and odour for oral administration with good patient compliance and acceptance, especially for children.
Clindamycin is available in the form of oral solution under the brand name of CLEOCIN PEDIATRIC® (Clindamycin) for pediatric patients in the dose of 75 mg/5 ml.
We have now surprisingly found that the unpleasant taste and odour of clindamycin could be substantially improved by the addition of an effective amount polyhydric alcohol in the composition while still maintaining the stability of the composition.
Further the invention provides simple and cost effective manufacturing methods for producing clindamycin composition(s) with good stability and organoleptic properties, and reduction in the total solid content of the composition compared to the marketed formulation.
Thus the invention provides composition(s) of clindamycin with an improved taste; substantially reduced unpleasant odour, and a pleasant mouth feel with substantially unchanged bioavailability using cost effective manufacturing methods.